To understand the cellular basis for control of Candida albicans growth in vitro, we developed a 24h radiolabel microassay that measures 3H-glucose uptake in residual candida and demonstrated that human polymorphonuclear neutrophils (PMN) and monocytes were primarily responsible for inhibiting candida growth. T cells and large granular lymphocytes (LGL) with NK function had no innate activity against candida. Interferon (IFN) and interleukin 2 (IL2) which activated NK function in LGL still did not activate LGL to inhibit candida growth. Stimulation of LGL with heat- killed candida also did not activate them to inhibit candida but their supernatant now contained soluble factors that enhanced PMN anticandida activity. This supernatant contained IFN and tumor necrosis factor which in the purified or recombinant form could activate PMN function. However, antibodies against IFN and TNF only partially inhibited the LGL supernatant factor(s) to stimulate PMN. Therefore, in addition to IFN and TNF, LGL could be activated by killed candida to release an unknown but potent PMN activating factors(s). We propose to continue to analyze the cellular interactions and the factors involved in inhibition of candida growth by 1) examining the mechanisms whereby IFN and TNF directly activate PMN, 2) identifying other cytokines and their mechanisms of activation of PMN, 3) determining the biochemical pathways that are activated in PMN by each cytokine, and 4) determining the source of PMN- activating factors and characterizing the putative novel factors unrelated to known cytokines that might be produced by LGL and other cells. The data gathered from this proposed study will help us gain some insight into the high efficiency of resistance to C. albicans infections in normal individuals and allow us to begin to identify which component of the PMN-lymphocyte linkage is missing or defective in certain diseases of the immunocompromised host that leads to persistent candidiasis.